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Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy

The major hurdle for cancer vaccines to be effective is posed by tumor immune evasion. Several common immune mechanisms and mediators are exploited by tumors to avoid immune destruction. In an attempt to shed more light on the immunosuppressive environment in uterine tumors, we analyzed the presence...

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Autores principales: Vanderstraeten, Anke, Luyten, Catherine, Verbist, Godelieve, Tuyaerts, Sandra, Amant, Frederic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024136/
https://www.ncbi.nlm.nih.gov/pubmed/24658839
http://dx.doi.org/10.1007/s00262-014-1537-8
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author Vanderstraeten, Anke
Luyten, Catherine
Verbist, Godelieve
Tuyaerts, Sandra
Amant, Frederic
author_facet Vanderstraeten, Anke
Luyten, Catherine
Verbist, Godelieve
Tuyaerts, Sandra
Amant, Frederic
author_sort Vanderstraeten, Anke
collection PubMed
description The major hurdle for cancer vaccines to be effective is posed by tumor immune evasion. Several common immune mechanisms and mediators are exploited by tumors to avoid immune destruction. In an attempt to shed more light on the immunosuppressive environment in uterine tumors, we analyzed the presence of PD-L1, PD-L2, B7-H4, indoleamine 2,3-dioxygenase (IDO), galectin-1, galectin-3, arginase-1 activity and myeloid-derived suppressor cell (MDSC) infiltration. IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemistry. PD-L2 was mostly expressed at low levels in these tumors. We found high IDO expression in 21 % of endometrial carcinoma samples and in 14 % of uterine sarcoma samples. For PD-L1 and B7-H4, we found high expression in 92 and 90 % of endometrial cancers, respectively, and in 100 and 92 % of the sarcomas. Galectin-1 and 3 were analyzed in tissue lysates by ELISA, but we did not find an increase in both molecules in tumor lysates compared with benign tissues. We detected expression of galectin-3 by fibroblasts, immune cells and tumor cells in single-cell tumor suspensions. In addition, we noted a highly significant increase in arginase-1 activity in endometrial carcinomas compared with normal endometria, which was not the case for uterine sarcomas. Finally, we could demonstrate MDSC infiltration in fresh tumor suspensions from uterine tumors. These results indicate that the PD-1/PD-L1 interaction and B7-H4 could be possible targets for immune intervention in uterine cancer patients as well as mediation of MDSC function. These observations are another step toward the implementation of inhibitors of immunosuppression in the treatment of uterine cancer patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1537-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-40241362014-05-29 Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy Vanderstraeten, Anke Luyten, Catherine Verbist, Godelieve Tuyaerts, Sandra Amant, Frederic Cancer Immunol Immunother Original Article The major hurdle for cancer vaccines to be effective is posed by tumor immune evasion. Several common immune mechanisms and mediators are exploited by tumors to avoid immune destruction. In an attempt to shed more light on the immunosuppressive environment in uterine tumors, we analyzed the presence of PD-L1, PD-L2, B7-H4, indoleamine 2,3-dioxygenase (IDO), galectin-1, galectin-3, arginase-1 activity and myeloid-derived suppressor cell (MDSC) infiltration. IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemistry. PD-L2 was mostly expressed at low levels in these tumors. We found high IDO expression in 21 % of endometrial carcinoma samples and in 14 % of uterine sarcoma samples. For PD-L1 and B7-H4, we found high expression in 92 and 90 % of endometrial cancers, respectively, and in 100 and 92 % of the sarcomas. Galectin-1 and 3 were analyzed in tissue lysates by ELISA, but we did not find an increase in both molecules in tumor lysates compared with benign tissues. We detected expression of galectin-3 by fibroblasts, immune cells and tumor cells in single-cell tumor suspensions. In addition, we noted a highly significant increase in arginase-1 activity in endometrial carcinomas compared with normal endometria, which was not the case for uterine sarcomas. Finally, we could demonstrate MDSC infiltration in fresh tumor suspensions from uterine tumors. These results indicate that the PD-1/PD-L1 interaction and B7-H4 could be possible targets for immune intervention in uterine cancer patients as well as mediation of MDSC function. These observations are another step toward the implementation of inhibitors of immunosuppression in the treatment of uterine cancer patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1537-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2014-03-22 2014 /pmc/articles/PMC4024136/ /pubmed/24658839 http://dx.doi.org/10.1007/s00262-014-1537-8 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article
Vanderstraeten, Anke
Luyten, Catherine
Verbist, Godelieve
Tuyaerts, Sandra
Amant, Frederic
Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title_full Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title_fullStr Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title_full_unstemmed Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title_short Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
title_sort mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024136/
https://www.ncbi.nlm.nih.gov/pubmed/24658839
http://dx.doi.org/10.1007/s00262-014-1537-8
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